(a) Field of the Invention
This invention relates to alkanoylpyridinones, their preparation and their use as cardiotonics.
(b) Description of the Prior Art
Sunthankar et al. [Indian J. of Chemistry 11, 1315-16 (1973)] show the reaction of cyanoacetamide with conjugated enol ethers, such as ethoxymethylenemalonate and analogous conjugated enol ethers to produce various substituted 2-pyridinones including 5-acetyl-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile and 5-acetyl-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarboxamide. No utility is shown for these compounds.
Kato et al. [J. Heterocyclic Chem. 18, 603-606 (1981)] show, inter alia, the dehydrogenation of 5-acetyl-3,4-dihydro-6-methyl-2(1H)-pyridinone by heating it with palladium black to produce 5-acetyl-6-methyl-2(1H)-pyridinone, which in turn is reacted with phosphorus oxychloride (phosphoryl chloride) to produce a mixture of 6-chloro-3-ethynyl-2-methylpyridine and 6-chloro-3-(1-chlorovinyl)-2-methylpyridine.
Kato et al. [Chem. Pharm. Bull. 17, 2411-2416 (1969)] disclose the preparation of 5-acetyl-3,4-dihydro-6-methyl-2(1H)-pyridinone in two ways: (a) by refluxing 4-oxo-2-penten-2-amine and acrylic anhydride in chloroform (75% yield); and (b) by heating 4-oxo-2-penten-2-amine and ethyl acrylate in ethanol containing sodium ethoxide (9% yield).
Example 13 of U.S. Pat. No. 3,654,291, issued Apr. 4, 1972, shows the reaction of 3-cyano-6-methyl-2(1H)-pyridinone with methylmagnesium iodide in benzene to produce 3-acetyl-6-methyl-2(1H)-pyridinone, which is then used as an intermediate to prepare the corresponding 3-acetyl-6-methyl-5-nitro-2(1H)-pyridinone, in turn, an intermediate for preparing the corresponding 5-amino compound, also used as an intermediate.
Fujita [Chem. Pharm. Bull. 23, 501-506 (1975)] in a chemical paper reporting the results of acylation of 1-alkyl-2(1H)-pyridinones by various means shows the preparation of various 5-acyl- and 3,5-diacyl-1-alkyl-2(1H)-pyridinones, including 5-acetyl-1-methyl-2(1H)-pyridinone and its 5-(RCO) homologs where R is C.sub.2 H.sub.5, C.sub.3 H.sub.7 and C.sub.4 H.sub.9. No pharmaceutical properties of these compounds are disclosed.
Krasnaya et al. [C.A. 87, 68099r (1977)] show, inter alia, the use of derivatives of ethyl 2-acetyl-5-amino-2,4-pentadienoate as an intermediate.